期刊
JOURNAL OF THE AMERICAN HEART ASSOCIATION
卷 11, 期 4, 页码 -出版社
WILEY
DOI: 10.1161/JAHA.121.024159
关键词
clopidogrel; pharmacogenetics
资金
- National Institutes of Health (NIH) [U01 HG007269, U01 HG007775, U01 HG007762, U01HG010245]
- NIH IGNITE Network
- NIH [R01 HL149752, T32 HG008958, K01 HL141690, U01 GM074492, U01 HL105198, UL1 TR002489, R01 HL092173, K24 HL133373, UL1 TR000165, UL1 TR0000005, U54 MD010723]
- University of Florida and its Clinical Translational Science Institute (NIH) [UL1 TR000064, UL1 TR001427]
- Penn Center for Precision Medicine at the Perelman School of Medicine at the University of Pennsylvania
- Hugh Kaul Precision Medicine Institute at the University of Alabama, Birmingham
- University of Pittsburgh/UPMC Institute for Precision Medicine
- American Society of Health System Pharmacists
- American Heart Association grant [17MCPRP33400175]
The clinical implementation of CYP2C19-guided antiplatelet therapy after PCI has shown better outcomes compared to clopidogrel treatment. For patients with a CYP2C19 loss-of-function variant, alternative therapy significantly reduces the risk of major atherothrombotic events.
Background Studies have demonstrated increased risk of major atherothrombotic events in CYP2C19 loss-of-function (LOF) variant carriers versus non-carriers treated with clopidogrel after percutaneous coronary intervention (PCI). We sought to evaluate real-world outcomes with the clinical implementation of CYP2C19-guided antiplatelet therapy after PCI. Methods and Results Data from 9 medical centers where genotyping was performed in the setting of PCI were included. Alternative therapy with prasugrel or ticagrelor was recommended for patients with a CYP2C19 LOF variant. The primary outcome was the composite of major atherothrombotic events (all-cause death, myocardial infarction, ischemic stroke, stent thrombosis, or hospitalization for unstable angina) within 12 months following PCI. Moderate or severe/life-threatening bleeding within 12 months was a secondary outcome. Among 3342 patients, 1032 (31%) were LOF carriers, of whom 571/1032 (55%) were treated with alternative therapy. In LOF carriers, the rate of major atherothrombotic events was lower in patients treated with alternative therapy versus clopidogrel (adjusted HR, 0.56; 95% CI 0.39-0.82). In those without a LOF allele, no difference was observed (adjusted HR, 1.07; 95% CI 0.71-1.60). There was no difference in bleeding with alternative therapy versus clopidogrel in either LOF carriers or those without a LOF allele. Conclusions Real-world data demonstrate lower atherothrombotic risk in CYP2C19 LOF carriers treated with alternative therapy versus clopidogrel and similar risk in those without a LOF allele treated with clopidogrel or alternative therapy. These data suggest that PCI patients treated with clopidogrel should undergo genotyping so that CYP2C19 LOF carriers can be identified and treated with alternative therapy.
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